Adetunji, Shakirat Adeola (2020-05). THE ROLE OF REGULATORY T CELLS IN THE PATHOGENESIS AND PERSISTENCE OF BRUCELLA ABORTUS IN THE REPRODUCTIVE SYSTEM OF FEMALE MICE. Doctoral Dissertation. Thesis uri icon

abstract

  • Stealthy intracellular bacterial pathogens are known to establish persistent and sometimes life-long infections. Some of these pathogens also have a tropism for the reproductive system thereby increasing the risk of reproductive disease and infertility. To date, the pathogenic mechanism involved remains poorly understood. Here, we demonstrated that Brucella abortus, a notorious reproductive pathogen, has the ability to infect the non-pregnant uterus, sustain infection, and induce inflammatory changes during both acute and chronic stages of infection. In addition, we discovered that chronically infected mice had a significantly reduced number of pregnancies compared to na?ve controls. To investigate the immunologic mechanism responsible for uterine tropism, we explored the role of regulatory T cells (Tregs) in the pathogenesis of Brucella abortus infection. We showed that highly suppressive CD4+FOXP3+TNFR2+ Tregs contribute to the persistence of Brucella abortus infection and that inactivation of Tregs with TNFR2 antagonistic antibody protected mice by significantly reducing bacterial burden both systemically and within reproductive tissues. These findings confirm a critical role for Tregs in the pathogenesis of persistence induced by B. abortus. Results from this study indicate that adverse reproductive outcomes can occur as sequelae of chronic Brucella infection in non-pregnant animals, and that fine-tuning Tregs activity may provide novel immunotherapeutic and prevention strategies against brucellosis and potentially other intracellular bacterial infections.

publication date

  • May 2020
  • May 2020
  • May 2020
  • May 2020
  • May 2020
  • May 2020